![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 18 to 42 of 125. Go back in thread:
Posted by cecilia on March 15, 2006, at 22:33:35
In reply to Re: Never thought I'd hear this..... » cecilia, posted by linkadge on March 15, 2006, at 9:32:25
Therapy is addicting for a lot of people. Even when it isn't helping, the more money and emotional emergy you put into it the harder it is to fold your cards and walk away. Emotionally the whole process can put you into a childlike state and just like a child will beg to stay with an abusive parent, many people will attach like glue to a therapist who doesn't help them at all. Cecilia
Posted by Dr. Bob on March 16, 2006, at 1:28:28
In reply to Psychotherapy addicting, posted by cecilia on March 15, 2006, at 22:33:35
> Therapy is addicting for a lot of people...
Sorry to interrupt, but I'd like to redirect follow-ups regarding therapy to Psycho-Babble Psychology. Here's a link:
http://www.dr-bob.org/babble/psycho/20060312/msgs/620831.html
Thanks,
Bob
Posted by SLS on March 16, 2006, at 6:23:57
In reply to Re: Never thought I'd hear this....., posted by linkadge on March 15, 2006, at 9:52:07
> The only thing wrong with labling antidepressant induced mania as bipolar is that it can force a patient to take heavy, and perhaps unnecssary medication.
This is where I think it is important to determine whether or not there are any other signs of bipolarity. It is a judgment call. The other consideration is that an algorithm be used in such cases such that "heavy" medication be used only if "lighter" treatments fail. Again, this is a judgment call.
> The thing that scares me the most, is that patients who have manic reactions to medications are often placed directly on mood stabalizers, before trying the grosly simplistic: simply tapering the antidepressant.
When I first became manic on antidepressants, I had been in remission - my only true remission - for about 6 months. Lithium was introduced and the antidepressants withdrawn. To make a long story short, I never responded to those same antidepressants again. The antidepressant response could not be recaptured. This is the risk taken when one discontinues effective drugs. Perhaps this applies to reduced dosages as well.
> I would also argue *against* the notion that a positive responce to mood stabalizers means that a person is bipolar.
Clinicians' experiences seem to controvert your conclusion.
> The reason being is that Dr. Manji's work again shows that lithium, depakote, and antipsychotics are able to block the behavioral reactions of mice to amphetamines and high dose antidepressants.
And...
> I.e. you take a normal (non-bipolar) mouse, you can make it manic with drugs, and you can block the manic reaction with mood stabalizers and antipsychotics.
Stereotypy is not mania. The rats do not become manic.
> Think of it this way. You can induce a seizure in just about anyone with the right drugs. Why is is so inconcievable that a manic episode is not just a branch of the same phenomina ?
The question is not whether or not such a thing is possible, it is what are the odds that a manic reaction to therapeutic dosages of antidepressants indicate bipolarity. My guess is that the odds are heavily in favor of bipolarity.
- Scott
Posted by linkadge on March 16, 2006, at 9:45:03
In reply to Re: Never thought I'd hear this..... » linkadge, posted by SLS on March 16, 2006, at 6:23:57
>This is where I think it is important to >determine whether or not there are any other >signs of bipolarity. It is a judgment call. The >other consideration is that an algorithm be used >in such cases such that "heavy" medication be >used only if "lighter" treatments fail. Again, >this is a judgment call.
That seems fair enough.
>When I first became manic on antidepressants, I >had been in remission - my only true remission - >for about 6 months. Lithium was introduced and >the antidepressants withdrawn. To make a long >story short, I never responded to those same >antidepressants again. The antidepressant >response could not be recaptured. This is the >risk taken when one discontinues effective >drugs. Perhaps this applies to reduced dosages >as well.
I would argue that the moment you went manic, was the real moment that the true antidepressant responce was gone forever.
>Clinicians' experiences seem to controvert your >conclusion.
Theres no way to proove that. So if a anti-manic agent blocks the antidepressant effect, and calms the person down (like it should) then we are to conclude that a person is bipolar. It is the logic that is used that is flawed. You can "respond" to a mood stabalizer insofar as it blocks the cycling that the antidepressant produced does not mean you would be cyling on your own.
>Stereotypy is not mania. The rats do not become >manic.Nor do they become depressed? If we throw away the mania model then we must throw away the depressed mouse model. Manic mice show many similarities to manic people. Decreased sleep, increased sexual persuit, increased risk taking, increased hedonic activities, agressivness, hyperlocomotion. As well, biochemically they exhibit similarities. Increased catecholamine release, PKC overexpression, certain patterns of epileptiform activity.
>The question is not whether or not such a thing >is possible, it is what are the odds that a >manic reaction to therapeutic dosages of >antidepressants indicate bipolarity. My guess is >that the odds are heavily in favor of bipolarity.My guess is that they are not. A lot of Dr. Manji's work shows that antidepressants activate some of the same pathways that are turned on in mania. For instance. TCA's increase PKC expression (dramatically). OTOH, PKC inhibitors are effective antimanic agents. Another thing that you have to consider is that antidepressants may me inducing *undetected* cylcing and hypomania in a lot of people.
Another thing to consider is that cumulative sleep deprivation can cause psychosis/mania in just about anyone, that is fairly documented. The TCA's can block certain sleep stages for a very long time. They're dirty drugs.
My mother had one manic episode (in reaction to a TCA which she took for about 6 months, and claimed it was the only time she felt good :)). I just don't see how that justifies a lifetime of lithium.Its my own personal experiement to prove this thing wrong. Maybe I will fail, and then I will accept treatment. I am going to proove that a single manic episode in responce to an antidepressant does not imply bipolar. So far (over 1 year off all treatment) has said to me that I don't cycle at all, but those are strong drugs.
Linkadge
Posted by SLS on March 16, 2006, at 9:51:49
In reply to Re: Never thought I'd hear this....., posted by linkadge on March 15, 2006, at 15:11:01
Are there any widely accepted rodent models of mania as there are with depression?
I think we can exclude stereotypy. If anything, it might represent schizophrenia or OCD. I don't think hyperlocomotion is valid either. Stimulants can produce increased activity in humans without producing mania. I would like to know what Dr. Manji considers to be an animal model of mania.
- Scott
Posted by SLS on March 16, 2006, at 10:36:57
In reply to Re: Never thought I'd hear this....., posted by linkadge on March 16, 2006, at 9:45:03
> I would argue that the moment you went manic, was the real moment that the true antidepressant responce was gone forever.
There may be some truth in your hypothesis. It almost fits the sequence of events that led up to the depression subsequent to my second manic reaction. I'll describe at greater length the specifics at some point in the future. I hope you are wrong, of course, but you may not be.
I am hoping that it was the subsequent pulsing of antidepressants that produced the treatment resistance. Unfortunately, my doctor at the time decided to try the newly-approved Prozac when I relapsed into depression. Then it was Parnate monotherapy. Then it was Nardil monotherapy. Then...
> > Stereotypy is not mania. The rats do not become manic.
> Nor do they become depressed?They exhibit their depressive behaviors in the absence of drugs.
> If we throw away the mania model then we must throw away the depressed mouse model.
This is the thing. To my knowledge, a rodent model of mania in the absence of drugs does not yet exist.
> Manic mice show many similarities to manic people. Decreased sleep, increased sexual persuit, increased risk taking, increased hedonic activities, agressivness, hyperlocomotion. As well, biochemically they exhibit similarities. Increased catecholamine release, PKC overexpression, certain patterns of epileptiform activity.
Also seen in non-manic humans taking amphetamines and cocaine, no?
I admit that I really don't know enough about this stuff. However, the question raised is whether or not a manic reaction to therapeutic dosages of antidepressants indicates bipolar disorder. I guess the best way to assess this question is via a longitudinal investigation of people who have experienced this reaction, both retrospectively and prospectively.
I'm trying to find some stuff on the Net that would indicate which animal model of mania is currently accepted. I know that Dr. Manji has suggested models to be used to evaluate treatments for mania, but this still does not represent an induction of a mania in association with an antidepressant. I have not read about a rodent displaying hyperlocomotion, hypersexuality, etc. as a reaction to an antidepressant. As a matter of fact, Dr. Manji demonstrated that amphetamine alone was not sufficient as a model of mania, despite its capacity to produce hyperlocomotion and stereotypy. He needed to create a hyperlocomotive state using a combination of amphetamine + chlordiazepoxide to produce a state that was responsive to valproate.
http://www.psychogenics.com/pdf/biploar-disorders.pdf
Can amphetamine alone switch someone from depression into mania?
The irony is this: Dr. Manji evaluates the validity of an animal model of mania by determining whether or not it is attenuated by a mood stabilizer. This is tantamount to diagnosing bipolar disorder by evaluating response vs non-response to a mood stabilizer.
- Scott
Posted by linkadge on March 16, 2006, at 10:56:49
In reply to Re: Never thought I'd hear this..... » linkadge, posted by SLS on March 16, 2006, at 9:51:49
I am aware of some animal models of mania. Rapid cycling, for instance, could easily be detected in animal. (Ie. they are hyperactive/hypersexual for days, and then seem to crash and not move for days)
I do know that there are big bucks put into reasearch nowadays to see how SSRI's can influence these behaviors, as well as influencing genes that have been linked with instability.
I know that there are animal models used which are often sucessfull at findind potential mood stabalizing agents. A dexamphetamine-chlordiazepoxide model was used to identify keppra as a potential mood stabilizer.
Methamphetamine is often used to replicate an animal model of mania with psychotic features.
There is some evidence that the GRK3 (G protein receptor kinase) enzyme is involved in mania, and perhaps psychosis. Expression is elevated in mania, and the state is readily reproducable in mice by administration of stimulants (don't know about antidepressants)
PACAP is another (enzyme?) that is influcenced oppositly by antidepressants and mood stabalizers, and is under investigation.
http://neurotransmitter.net/bipolargrk3.html
Pertaining to SSRI induced mania and rapid cylcing.
http://neurotransmitter.net/admania.html
Linkadge
Posted by SLS on March 16, 2006, at 11:23:33
In reply to Re: Never thought I'd hear this....., posted by linkadge on March 16, 2006, at 10:56:49
Hi.
The links you gave here seem to be very helpful. Thanks. I'll have to look at them later.
Again, I think that the majority of manic reactions to antidepressants are indicative of a bipolar diathesis and that using amphetamines in animals is not a valid reproduction of this process.
- Scott
> I am aware of some animal models of mania. Rapid cycling, for instance, could easily be detected in animal. (Ie. they are hyperactive/hypersexual for days, and then seem to crash and not move for days)
>
> I do know that there are big bucks put into reasearch nowadays to see how SSRI's can influence these behaviors, as well as influencing genes that have been linked with instability.
>
> I know that there are animal models used which are often sucessfull at findind potential mood stabalizing agents. A dexamphetamine-chlordiazepoxide model was used to identify keppra as a potential mood stabilizer.
>
> Methamphetamine is often used to replicate an animal model of mania with psychotic features.
>
> There is some evidence that the GRK3 (G protein receptor kinase) enzyme is involved in mania, and perhaps psychosis. Expression is elevated in mania, and the state is readily reproducable in mice by administration of stimulants (don't know about antidepressants)
>
> PACAP is another (enzyme?) that is influcenced oppositly by antidepressants and mood stabalizers, and is under investigation.
>
> http://neurotransmitter.net/bipolargrk3.html
>
> Pertaining to SSRI induced mania and rapid cylcing.
>
> http://neurotransmitter.net/admania.html
>
>
> Linkadge
>
>
>
>
>
Posted by linkadge on March 16, 2006, at 11:28:39
In reply to Re: Never thought I'd hear this..... » linkadge, posted by SLS on March 16, 2006, at 10:36:57
>They exhibit their depressive behaviors in the >absence of drugs.
Most of the time we induce depression in animals by subjecting them to repeated mild, chronic stressors. Genetically speaking, I am only aware of the flinders rats, which still really only exhibit depression in response to cholinergic drugs.
>This is the thing. To my knowledge, a rodent >model of mania in the absence of drugs does not >yet exist.I would argue that an animal model of depression, in the absence of chronic stressors, doesn't really exist.
>Also seen in non-manic humans taking >amphetamines and cocaine, no?I don't know what you would classify it as, but if a drug induced lack of sleep, hypersexuality, hyperhedonia, hallucinations, euphoria, hyperlocomotion, then I would say that drug has induced a manic episode.
>I admit that I really don't know enough about >this stuff. However, the question raised is >whether or not a manic reaction to therapeutic >dosages of antidepressants indicates bipolar >disorder. I guess the best way to assess this >question is via a longitudinal investigation of >people who have experienced this reaction, both >retrospectively and prospectively.I see it as a continuoum. Especially when we are talking about norepinephrine active drugs, we see
a lot of behaviors such as irritability in people taking the drug for depression, even if they never get diagnosed with mania. Its like steroids, a lot of the problems associated with them are dose dependant, and also dependant on individual tolerances. A theraputic dose doesn't really mean anything in my oppinion. By friend can drink 10 cups of coffee and not get anxious, I drink 1 and have a panic attack. But, off coffee, I don't have those panic attacks.>He needed to create a hyperlocomotive state >using a combination of amphetamine + >chlordiazepoxide to produce a state that was >responsive to valproate.
I think that it depends on the animal, and the situation. Stress increases PKC, and antidepressants increase PKC, so it could be additive. I personally noted that my "manic episode" was a combination of severe stress, and high doses of antidepressants. There are so many factors.
>Can amphetamine alone switch someone from >depression into mania?
I would say so. Perhaps high doses would be needed.
>The irony is this: Dr. Manji evaluates the >validity of an animal model of mania by >determining whether or not it is attenuated by a >mood stabilizer. This is tantamount to >diagnosing bipolar disorder by evaluating >response vs non-response to a mood stabilizer.
That is exactly my point. If mood stabalizers serve as antidotes to manic episodes (of any origin), then there is no way to determine what exactly caused the manic episode. I heard of a lady who treated her "bipolar disorder" with antidepressants alone. If she felt a manic epsiode coming on, she simply lowered the antidepressant dose.
Here is another interesting article. It suggests how elevated PKC can cause impaired thinking, impaired memory, and impulsivity. At the bottom, it notes how it was able to create these conditions using norepinephrine active drugs, (if I recall it was an NRI used) It basically said how lithium or tegretol were able to block the effects of norepinephrine drugs in these domains.
http://www.nimh.nih.gov/press/prenzyme.cfm
Linkadge
Posted by detroitpistons on March 16, 2006, at 12:33:52
In reply to Re: Never thought I'd hear this..... » detroitpistons, posted by SLS on March 14, 2006, at 13:00:10
Scott/ Link,
As you (Scott) mentioned, early onset (before the age of 25) of episodes is pretty widely accepted as a soft sign of bipolar. This was the case with me. I've read that cyclothymic and dysthymic temperament early on is also suggestive of bipolar predisposition. This describes me during my adolescence, with major depression occurring a bit later on (early twenties). Also, I've read that most bipolar II patients with early onset had several episodes of depression before ever becoming hypomanic. This also describes me. I'm not saying that I'm yet completely convinced that I have bipolar II. I found the following interesting:
BP-H AA refers to antidepressant associated hypomania.
"LIMITATION: Naturalistic study, where treatment was uncontrolled."
"BP-H AA emerges as a disorder with depressive temperamental instability, manifesting hypomania later in life (and, by definition, during pharmacotherapy only). By the standards of clinicians who have taken care of these patients for long periods of time, BP-H AA appears as no less bipolar than those with prototypical BP-II. We submit that familial bipolarity ('genotypic' bipolarity) strongly favors their inclusion within the realm of bipolar II spectrum, as a prognostically less favorable depression-prone phenotype of this disorder, and which is susceptible to destabilization under antidepressant treatment. These considerations argue for revisions of DSM-IV and ICD-10 conventions. BP-HAA may represent a genetically less penetrant expression of BP-II; phenotypically; it might provisionally be categorized as bipolar III." [Abstract]
For me, I think the most important part of this is, "By the standards of clinicians who have taken care of these patients for long periods of time, BP-H AA appears as no less bipolar than those with prototypical BP-II."
Personally, I put more stock into clinician experience, expecially when it is over long periods of time with the same patients.
Here's the abstract in it's entirety"
Akiskal HS, Hantouche EG, Allilaire JF, Sechter D, Bourgeois ML, Azorin JM, Chatenet-Duchene L, Lancrenon S.
Validating antidepressant-associated hypomania (bipolar III): a systematic comparison with spontaneous hypomania (bipolar II).
J Affect Disord. 2003 Jan;73(1-2):65-74."BACKGROUND: According to DSM-IV and ICD-10, hypomania which occurs solely during antidepressant treatment does not belong to the category of bipolar II (BP-II). METHODS: As part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 144 (29.2%) fulfilled the criteria for bipolar II with spontaneous hypomania (BP-II Sp), and 52 (10.5%) had hypomania associated solely with antidepressants (BP-H AA). RESULTS: BP-II Sp group had earlier age at onset, more hypomanic episodes, and higher ratings on cyclothymic and hyperthymic temperaments, and abused alcohol more often. The two groups were indistinguishable on the hypomania checklist score (12.2+/-4.0 vs. 11.4+/-4.4, respectively, P=0.25) and on rates of familial bipolarity (14.1% vs. 11.8%, respectively, P=0.68). But BP-H AA had significantly more family history of suicide, had higher ratings on depressive temperament, with greater chronicity of depression, were more likely to be admitted to the hospital for suicidal depressions, and were more likely to have psychotic features; finally, clinicians were more likely to treat them with ECT, lithium and mood stabilizing anticonvulsants. LIMITATION: Naturalistic study, where treatment was uncontrolled. CONCLUSION: BP-H AA emerges as a disorder with depressive temperamental instability, manifesting hypomania later in life (and, by definition, during pharmacotherapy only). By the standards of clinicians who have taken care of these patients for long periods of time, BP-H AA appears as no less bipolar than those with prototypical BP-II. We submit that familial bipolarity ('genotypic' bipolarity) strongly favors their inclusion within the realm of bipolar II spectrum, as a prognostically less favorable depression-prone phenotype of this disorder, and which is susceptible to destabilization under antidepressant treatment. These considerations argue for revisions of DSM-IV and ICD-10 conventions. BP-HAA may represent a genetically less penetrant expression of BP-II; phenotypically; it might provisionally be categorized as bipolar III." [Abstract]
> > > I guess you'll know soon what psychological issues remain after the depression goes into remission. Sometimes, depression leaves a real mess in its wake. Therapy can help clean it up after the depression is gone. Sometimes, "issues" mysteriously vanish once the depression is gone. I guess your doctor would like to see you biologically healthy before assessing your psychological health.
> > >
> > > With depression, things generally are not that simple. I don't think there are very many blanket statements that can be made that covers every person who suffers from it. Let's hope the Lamictal does the trick.
> > >
> > > Are you bipolar? What other drugs, if any, are you currently taking.
> > >
> > > Good luck.
> > >
> > >
> > > - Scott
> > >
> >
> > I was recently diagnosed as bipolar II after being on Effexor 225mg. I had an irritable hypomania with a lot of agitation, irritability, racing thoughts, excess energy, etc. I was sort of rapid cycling and a kind of mixed state.
> >
> > I went down to 150mg of Effexor and started the Lamictal (just went up to 200mg today). The doc wants to wait till I'm fully stabilized to think about taking me off of Effexor.
> >
> > To be honest, I'm not really sure I'm really bipolar because this hypomanic episode happened while on Effexor. But I did take Effexor once before with awesome results (maybe even some euphoric hypomania, but I can't really remember)and then it pooped out. I then tried Paxil and then Lexapro, with diminishing results.
> >
> > Late last summer, I started becoming depressed again, and saw the doc but by that time I was really spiralling down. The Effexor succeeded in pulling me up, but then a couple months later the hypomania hit me hard. I guess the fact that my depression is recurring along with the fact that SSRI's don't work for me are soft signs of bipolar, but I'm still not completely convinced of the BPII dx.
>
> I, too, have experienced mania only while taking antidepressants. That seems to be enough to qualify one as having a bipolar-spectrum disorder. For the most part, I would agree with this diagnosis.
>
> 200mg seems to be the "sweet spot" for Lamictal when it is used to treat bipolar depression. For me, Lamictal by itself is not sufficient to treat depression. It does seem to be used more often as an augmenting agent than as monotherapy. However, there have been a few postings here on Psycho-Babble by people for whom Lamictal was sufficient to bring them into remission. Interindividual biologies are so varied as to produce many different responses to the same medication. It is still difficult to predict how any one person will react to any one treatment.
>
> I am not one who believes that psychotherapy is necessary simply because one describes themselves as being depressed, especially if the depression is part of a bipolar diathesis. Some perfectly healthy people are struck with brain disorders in the absence of psychopathology.
>
> I suspect that you have been in psychotherapy long enough to have identified specific issues that need attention - if any do indeed exist. For me, I have used psychotherapy from time to time to help me deal with the effects that bipolar depression has had on my life. It has helped provide me with some tools to "undo" the damage that the biological depression has caused and continues to inflict. I seem to have very few issues that are independent of bipolar disorder. For these, I have used pschotherapy as a precision tool. However, I do believe that issues can be resolved, and not be vortices of perpetual therapeutic need. It has been my experience that during times of remission, I have not had a need for psychotherapy. I pretty much just get up, brush myself off, and start walking and talking. I have fun.
>
> It might be interesting for you to identify your psychological issues and describe them to your doctor. Perhaps he will conclude that you should go for psychotherapy. Perhaps not. Either way, you will have provided him with detail that he didn't have before from which to draw more informed conclusions as to how to approach your recovery from depression and maintenance of mental hygeine.
>
> If I were a doctor, I would never resolve to never tell anyone that they don't need psychotherapy. Some people don't.
>
> :-)
>
>
> - Scott
>
Posted by detroitpistons on March 16, 2006, at 12:51:41
In reply to Re: Never thought I'd hear this....., posted by linkadge on March 16, 2006, at 11:28:39
Link,
> >Also seen in non-manic humans taking >amphetamines and cocaine, no?
>
> I don't know what you would classify it as, but if a drug induced lack of sleep, hypersexuality, hyperhedonia, hallucinations, euphoria, hyperlocomotion, then I would say that drug has induced a manic episode.Link, just to give you a bit of my own experience, I've done drugs like cocaine and ecstasy recreationally, and I would most definitely think that the high mirrors mania completely in myself (at least the euphoric part of mania).
As a side note, after taking these drugs, I would crash incredibly hard, much much harder than any of the other people who took them with me. Also, my high seemed to be much more intense and pleasurable than theirs. They seemed to experience little, if any effect on mood even immediately (morning, or more accurately, afternoon after) after the high wore off. It would take me days to recover after taking these drugs. In one case, a major depression started a couple weeks after having done cocaine all night. Of course, this could be purely coincidence.
> >They exhibit their depressive behaviors in the >absence of drugs.
>
> Most of the time we induce depression in animals by subjecting them to repeated mild, chronic stressors. Genetically speaking, I am only aware of the flinders rats, which still really only exhibit depression in response to cholinergic drugs.
>
>
> >This is the thing. To my knowledge, a rodent >model of mania in the absence of drugs does not >yet exist.
>
> I would argue that an animal model of depression, in the absence of chronic stressors, doesn't really exist.
>
>
> >Also seen in non-manic humans taking >amphetamines and cocaine, no?
>
> I don't know what you would classify it as, but if a drug induced lack of sleep, hypersexuality, hyperhedonia, hallucinations, euphoria, hyperlocomotion, then I would say that drug has induced a manic episode.
>
>
> >I admit that I really don't know enough about >this stuff. However, the question raised is >whether or not a manic reaction to therapeutic >dosages of antidepressants indicates bipolar >disorder. I guess the best way to assess this >question is via a longitudinal investigation of >people who have experienced this reaction, both >retrospectively and prospectively.
>
> I see it as a continuoum. Especially when we are talking about norepinephrine active drugs, we see
> a lot of behaviors such as irritability in people taking the drug for depression, even if they never get diagnosed with mania. Its like steroids, a lot of the problems associated with them are dose dependant, and also dependant on individual tolerances. A theraputic dose doesn't really mean anything in my oppinion. By friend can drink 10 cups of coffee and not get anxious, I drink 1 and have a panic attack. But, off coffee, I don't have those panic attacks.
>
>
>
> >He needed to create a hyperlocomotive state >using a combination of amphetamine + >chlordiazepoxide to produce a state that was >responsive to valproate.
>
> I think that it depends on the animal, and the situation. Stress increases PKC, and antidepressants increase PKC, so it could be additive. I personally noted that my "manic episode" was a combination of severe stress, and high doses of antidepressants. There are so many factors.
>
> >Can amphetamine alone switch someone from >depression into mania?
>
> I would say so. Perhaps high doses would be needed.
>
> >The irony is this: Dr. Manji evaluates the >validity of an animal model of mania by >determining whether or not it is attenuated by a >mood stabilizer. This is tantamount to >diagnosing bipolar disorder by evaluating >response vs non-response to a mood stabilizer.
>
> That is exactly my point. If mood stabalizers serve as antidotes to manic episodes (of any origin), then there is no way to determine what exactly caused the manic episode. I heard of a lady who treated her "bipolar disorder" with antidepressants alone. If she felt a manic epsiode coming on, she simply lowered the antidepressant dose.
>
> Here is another interesting article. It suggests how elevated PKC can cause impaired thinking, impaired memory, and impulsivity. At the bottom, it notes how it was able to create these conditions using norepinephrine active drugs, (if I recall it was an NRI used) It basically said how lithium or tegretol were able to block the effects of norepinephrine drugs in these domains.
>
> http://www.nimh.nih.gov/press/prenzyme.cfm
>
>
> Linkadge
>
>
Posted by linkadge on March 16, 2006, at 13:49:37
In reply to Re: Never thought I'd hear this..... » linkadge, posted by detroitpistons on March 16, 2006, at 12:51:41
Not saying that this couldn't be indicitive of something, but I don't know if it is conclusive.
Recretional drugs are meant to make you high. Perhaps your friends are just less sensitive than you are :)
There are tons of reasons why depression can happen in early years. Depression is not uncommon in this agegroup. There are hormonal reasons, as well as social, and acedemic reasons. My brother was teased till the point that he developed major depression. Early onset, but he's not bipolar.
Like I said before, its not for me to make any judgement. These diseases are very complex.
I personally didn't care much about diagnosis so long as I found meds that helped.
Linkadge
Posted by gardenergirl on March 16, 2006, at 14:33:35
In reply to Re: Never thought I'd hear this....., posted by linkadge on March 16, 2006, at 13:49:37
I haven't read this whole thread, but I just wanted to give props to y'all for having such a great and civil discussion. The mutual respect you have for each other comes through loud and clear.
Thanks!
gg
Posted by SLS on March 16, 2006, at 16:07:47
In reply to Re: Never thought I'd hear this....., posted by linkadge on March 16, 2006, at 11:28:39
Hi Linkadge.
Thanks again for the link.
I have yet to review the others you posted.
You make some very valid points. I would be more convinced if I were to see a rat made "manic" by administering a SSRI or TCA.
I'll have to ponder whether or not a cocaine high resembles a true mania. On the surface, the descriptions of the experiences are similar. I have never experienced a cocaine high to be able to compare them. I tried it once as an experiment. It did nothing for me.
You know, it might be interesting to discuss the persistence of a manic reaction beyond the elimination of the drug. How long does a cocaine high last for once the cocaine is discontinued. How long does a manic reaction to an AD last once it is discontinued?
- Scott
Posted by detroitpistons on March 16, 2006, at 16:09:51
In reply to Re: Never thought I'd hear this....., posted by linkadge on March 16, 2006, at 13:49:37
> Not saying that this couldn't be indicitive of something, but I don't know if it is conclusive.
>I'm not convinced of anything one way or the other at this point. I'm just trying to find out as much as I can and look at both sides of the equation.
> Recretional drugs are meant to make you high. Perhaps your friends are just less sensitive than you are :)
>Could be...I was just throwing that out there to see what you guys thought. I just get the feeling that this happens because there is a very tenuous and fragile balance in my brain.
> There are tons of reasons why depression can happen in early years. Depression is not uncommon in this agegroup. There are hormonal reasons, as well as social, and acedemic reasons. My brother was teased till the point that he developed major depression. Early onset, but he's not bipolar.
>That's also entirely reasonable and possible. Although I seem to get depressed for no apparent reason. A couple times there's been a trigger, a couple times not.
Right now I'm split between unipolar vs bipolar II. Actually, I'm leaning ever so slightly towards the BPII simply because there are so many "soft" signs. For example, antidepressants worked for me the first time, and then all subsequent trials more or less failed, the last one bringing on hypomania. According to a prominent doctor who specializes in BPII (Dr. Phelps -- www.psycheducation.org), this would be a very typical pattern for BPII patients. He is basing this from his experience with many BPII patients....
Again, all of this isn't enough to fully convince me. I sway back and forth between the two extremes. Only time will tell what the truth is.
> Like I said before, its not for me to make any judgement. These diseases are very complex.
>
> I personally didn't care much about diagnosis so long as I found meds that helped.
>I agree on the one hand, but on the other hand I'm impatient to either validate or rule out this diagnosis. I shouldn't be impatient because it's not going to change anything, but that's my stubborn nature I guess.
Thanks for your input, Link. It keeps my views more balanced.
Posted by detroitpistons on March 16, 2006, at 16:37:59
In reply to Re: Never thought I'd hear this....., posted by SLS on March 16, 2006, at 16:07:47
> I'll have to ponder whether or not a cocaine high resembles a true mania.
I've never been delusional or had psychotic symptoms while on coke. But it was very euphoric with rapid and excessive speech, happiness, optimism, flight of ideas, expansive mood, grandiosity (extremely high confidence), tons of energy, extreme desire to socialize, increased interest in sex, psychomotor agitation, feeling that your thoughts are very lucid and you are brilliant.
On the surface, the descriptions of the experiences are similar. I have never experienced a cocaine high to be able to compare them. I tried it once as an experiment. It did nothing for me.
>You should have taken more. Just kidding ;)
> You know, it might be interesting to discuss the persistence of a manic reaction beyond the elimination of the drug. How long does a cocaine high last for once the cocaine is discontinued. How long does a manic reaction to an AD last once it is discontinued?
>Depending on the strength, it can last anywhere from 30 minutes to more than an hour after it is snorted. I don't know this from experience, but crack lasts for even less time. Generally, these manic-like symptoms fade away with the high.
Ecstasy lasts several hours and the manic-like symptoms also leave with the high. For me, I get severely depressed (more than anybody else that I know of) when the high is finished. It's almost like an accelerated cycling from mania to depression, or a microcosm of the entire process.
Posted by linkadge on March 16, 2006, at 16:57:49
In reply to Re: Never thought I'd hear this..... » linkadge, posted by detroitpistons on March 16, 2006, at 16:09:51
>I'm not convinced of anything one way or the >other at this point. I'm just trying to find out >as much as I can and look at both sides of the >equation.
Thats the right thing to do.
>Could be...I was just throwing that out there to >see what you guys thought. I just get the >feeling that this happens because there is a >very tenuous and fragile balance in my brain.For me, personaly, what I didn't like about the bipolar diagnosis was that the mood stabalizers just left me flat. They were never able to target things like anhedonia, and they never got me feeling back to myself. I think that may be more diagnositc of bipolar, when a mood stabalizer helps the depression too. (but I don't know about that idea)
>That's also entirely reasonable and possible. >Although I seem to get depressed for no apparent >reason. A couple times there's been a trigger, a >couple times not.
I know what you're saying.
>Right now I'm split between unipolar vs bipolar >II. Actually, I'm leaning ever so slightly >towards the BPII simply because there are so >many "soft" signs. For example, antidepressants >worked for me the first time, and then all >subsequent trials more or less failed, the last >one bringing on hypomania. According to a >prominent doctor who specializes in BPII (Dr. >Phelps -- www.psycheducation.org), this would be >a very typical pattern for BPII patients. He is >basing this from his experience with many BPII >patients....
The mania may be more indictive. The fact that a drug poops out - I don't know. Antidepressant poop out is a lot more common that admitted to by doctors. They poop out left and right for unipolar people too. I am personally fairly antidepressant resistant, but there have been quite a few times where my depression actually improved when coming *off* an AD, such as the last time.
>Again, all of this isn't enough to fully >convince me. I sway back and forth between the >two extremes. Only time will tell what the truth >is.
Bingo.
>I agree on the one hand, but on the other hand >I'm impatient to either validate or rule out >this diagnosis. I shouldn't be impatient because >it's not going to change anything, but that's my >stubborn nature I guess.I know what you're saying. I think a lot of us fit into categories of our own. I started feeling better the day I said WTF, who says I have to fit into this category? I personally think that a lot of the recent changes in psychatric thinking are really just a front to try and accomodate the strange, unexpected, and bizzare outcomes that have resulted from their theories. Remember, the drugs came first, the theories to explain their actions second.
If you make med changes slowly (I can never do that myself) it will probably lead to a better outcome in my opinion.
>Thanks for your input, Link. It keeps my views >more balancedNo problem. I wouldn't want you to take just my view anyway.
Linkadge
Posted by linkadge on March 16, 2006, at 17:04:37
In reply to Re: Never thought I'd hear this..... » SLS, posted by detroitpistons on March 16, 2006, at 16:37:59
>How long does a manic reaction to an AD last >once it is discontinued?
Thats my point, a lot of patients aren't given the chance to find out. They are slapped with a bipolar disgnosis, and thats that.
If I recall, Larry had a bad reaction to Luvox, I assume it remitted once he discontinued. One of my reactions to a medication remitted with discontinuation. I would hate to think that my mother went through 25 years of lithium when a simply coming of the TCA would have sufficed.
Linkadge
Posted by SLS on March 17, 2006, at 7:38:46
In reply to Re: Never thought I'd hear this....., posted by linkadge on March 16, 2006, at 11:28:39
> That is exactly my point. If mood stabalizers serve as antidotes to manic episodes (of any origin), then there is no way to determine what exactly caused the manic episode.
My point is this: The cluster of behaviors that we see with the administration of amphetamine, and that you have listed, is not a sufficient criterion for true mania such that these investigators needed to find other models to use. They judged the validity of their models based upon the capacity of mood stabilizers to reverse them. The hyperlocomotive and hyperlibidinal effects produced by psychostimulants are thus not equivalent to mania, and the presence of these behaviors is not sufficient to presume a valid animal model. Otherwise, I imagine they would have used cocaine. So far, I don't believe that they have been able to reproduce mania in rodents using SSRIs. Hopefully, they will develop a strain of rodent that exhibits such a reaction so as to serve as a model for mania. Of course, this would only go to reinforce the notion that there must be a genetic bipolar diathesis present to display a manic reaction to antidepressants.
My mania lasted for weeks after the antidepressants were discontinued, despite lithium treatment. I think this is one factor that leads me to believe that a manic reaction to antidepressants is fundamentally different from the acute behavioral states produced by psychostimulants. Mania involves a self-perpetuating process, most likely effected by kindling and probably facilitated through second messenger events. My guess is that antidepressant-induced mania gains inertia the longer it is allowed to continue. The sooner it is recognized and the offending drugs discontinued, the more quickly the mania will dissipate.
I wish Depakote were around when I became manic the first time. I believe that it would have been best if I were allowed to continue taking the antidepressants and just have added Depakote. My current treatment resistance probably developed because Nardil was given and withdrawn multiple times within a short period of time and the precipitation of severe mania followed by severe depression on each occassion. Again, Depakote would have prevented this as my mania are very responsive to it. It is also responsive to Zyprexa, but not to the older APs. I should think that combining Nardil and Zyprexa would be a great combination for bipolar depression.
I'm not saying that it is impossible for an SSRI to produce a manic reaction in someone who is not bipolar. Prednisone seems to be sufficient to do that. However, I think the odds are that for someone who has an affective disorder, the precipitation of mania by the administration of an antidepressant is reflective of bipolar disorder.
- Scott
Posted by linkadge on March 17, 2006, at 9:55:15
In reply to Re: Never thought I'd hear this..... » linkadge, posted by SLS on March 17, 2006, at 7:38:46
>My point is this: The cluster of behaviors that >we see with the administration of amphetamine, >and that you have listed, is not a sufficient >criterion for true mania such that these >investigators needed to find other models to use.
Some of the models we have today may not be conclusive, but I don't think that is reason to ignore them.
>They judged the validity of their models based >upon the capacity of mood stabilizers to reverse >them. The hyperlocomotive and hyperlibidinal >effects produced by psychostimulants are thus >not equivalent to mania, and the presence of >these behaviors is not sufficient to presume a >valid animal model.
Psychosis and mania have been effectively treated with drugs that were active in these paradigms.
We can aruge that these behaviors aren't identical to human mania, but we could argue the same thing for rodent depression. That doesn't negate the fact that the model is oftentimes highly predictive of drug sucess in humans.
>Otherwise, I imagine they would have used >cocaine. So far, I don't believe that they have >been able to reproduce mania in rodents using >SSRIs.I don't know.
>Hopefully, they will develop a strain of
>rodent that exhibits such a reaction so as to >serve as a model for mania. Of course, this >would only go to reinforce the notion that there >must be a genetic bipolar diathesis present to >display a manic reaction to antidepressants.It is my contention that long term rat studies may show things that the short term ones don't. Rat studies are brief, but in yours and my mothers case, a manic reaction was not evident right away.
>My mania lasted for weeks after the >antidepressants were discontinued, despite >lithium treatment.
Hey I've got a good one for you. An interesting phenomina, is that sometimes severe manic episodes can happen upon *discontinuation* of an antidepressant. Now would these people be bipolar? I would argue no. They are undergoing a dopamine rebound. Regular people + dopamine overflow = strange behavior.
>I think this is one factor
>that leads me to believe that a manic reaction >to antidepressants is fundamentally different >from the acute behavioral states produced by >psychostimulants. Mania involves a self->perpetuating process, most likely effected by >kindling and probably facilitated through second >messenger events.Stimulants can cause seizures in no time at all. I guess that implies they can cause kindling in no time at all too?
>My guess is that
>antidepressant-induced mania gains inertia the >longer it is allowed to continue. The sooner it >is recognized and the offending drugs >discontinued, the more quickly the mania will >dissipate.This is probably true.
>Again, Depakote would have prevented this as my >mania are very responsive to it. It is also >responsive to Zyprexa, but not to the older APs. >I should think that combining Nardil and Zyprexa >would be a great combination for bipolar >depression.
Depakote can be helpfull. It has a stronger anti-kindling effect than lithium. Lithium can actually be proconvulsant.
>I'm not saying that it is impossible for an SSRI >to produce a manic reaction in someone who is >not bipolar. Prednisone seems to be sufficient >to do that. However, I think the odds are that >for someone who has an affective disorder, the >precipitation of mania by the administration of >an antidepressant is reflective of bipolar >disorder.
I think that the moment we understand how these drugs work, is the moment we can quantify (with any certainty) how and why they fail.
Linkadge
Posted by Sobriquet Style on March 17, 2006, at 11:08:40
In reply to Re: Never thought I'd hear this....., posted by linkadge on March 16, 2006, at 16:57:49
>For me, personaly, what I didn't like about the bipolar diagnosis was that the mood stabalizers just left me flat.
This is very common with anyone suffering from bipolar disorder - the flat effect. Many people report that their mood is left flat with treatment for bipolar dioorder, whether it be Bipolar 1, 2 3, or whatever it maybe suggested the type is.
I think this because some view this as a side effect. Personally I view this as "the effect" in so far as with manic depression, one of differences with the illness compared with other illness is the cycling. The person may cycle in days, but more often the cycles of depression will last months. The hypo/mania's usually last not as long as the depressions, sometimes days. Everyone different. But the flat effect is common.
I think this is because science has looked at manic depression similar how one would a graph when looking at the mood swings. They see the up and down nature of the cycles and so with the drugs used today they have flat-lined it.
I think in the general population of people without psychiatric illness, many do not always feel flat. Especially not on a dialy basis. Unfortunately for those with bipolar disorder the remission of symptoms that come with the use of a mood stabilizer, means that the flat effect is the way the medication works to make the patient "normally mentally fundctioning" Like I say though, normal people do not experience flat effects of their emotions, in the same way manic depressives are not genetically geared up for it either.
The first line medications which are considered the best because they can stop cyling, are also the ones that cause the worst kind of flat effect in my opinon. Now, does the future hold a treatment with the same level of effect that can stop the cyling without the flatness? If I invested in pharmaceuticals, I'd certainly invest in that bipolar medication..
~
Posted by detroitpistons on March 17, 2006, at 11:22:58
In reply to Re: Never thought I'd hear this....., posted by Sobriquet Style on March 17, 2006, at 11:08:40
Hi,
I've been taking Lamictal along with Effexor, and I don't feel flat at all. Perhaps this is just because the Lamictal didn't completely eliminate the hypomania, and I'm still in an "up" phase.
> >For me, personaly, what I didn't like about the bipolar diagnosis was that the mood stabalizers just left me flat.
>
> This is very common with anyone suffering from bipolar disorder - the flat effect. Many people report that their mood is left flat with treatment for bipolar dioorder, whether it be Bipolar 1, 2 3, or whatever it maybe suggested the type is.
>
> I think this because some view this as a side effect. Personally I view this as "the effect" in so far as with manic depression, one of differences with the illness compared with other illness is the cycling. The person may cycle in days, but more often the cycles of depression will last months. The hypo/mania's usually last not as long as the depressions, sometimes days. Everyone different. But the flat effect is common.
>
> I think this is because science has looked at manic depression similar how one would a graph when looking at the mood swings. They see the up and down nature of the cycles and so with the drugs used today they have flat-lined it.
>
> I think in the general population of people without psychiatric illness, many do not always feel flat. Especially not on a dialy basis. Unfortunately for those with bipolar disorder the remission of symptoms that come with the use of a mood stabilizer, means that the flat effect is the way the medication works to make the patient "normally mentally fundctioning" Like I say though, normal people do not experience flat effects of their emotions, in the same way manic depressives are not genetically geared up for it either.
>
> The first line medications which are considered the best because they can stop cyling, are also the ones that cause the worst kind of flat effect in my opinon. Now, does the future hold a treatment with the same level of effect that can stop the cyling without the flatness? If I invested in pharmaceuticals, I'd certainly invest in that bipolar medication..
>
> ~
>
>
Posted by Sobriquet Style on March 17, 2006, at 11:52:49
In reply to Re: Never thought I'd hear this..... » Sobriquet Style, posted by detroitpistons on March 17, 2006, at 11:22:58
>I've been taking Lamictal along with Effexor, and I don't feel flat at all. Perhaps this is just because the Lamictal didn't completely eliminate the hypomania, and I'm still in an "up" phase.
Sounds better than being left in a down phase :-)
I think you're probably right about Lamictal and the hypomania, Lamotrigine seems rare in the case that it is effectively good for treating depression and in some respects is therefore seen as an antidepressant rather than a mood stabilizer as its rarely effective (if at all) for acute mania and in some cases it doesn't look that good for preventing mania. That said bipolar depression is a disgusting depression to say the least, so its a great tool to fight it.
I'm currently taking Lamictal myself, it kind of feels more like an antidepressant to me compared to a mood stabilizer. It does stabilize, but I wouldn't say I feel protected from the high's too much and it appears to increase anxiety related symptoms. I'm only taking 12.5mg because when I push the dosage up it makes me feel pretty uncomfortable.
~
Posted by SLS on March 17, 2006, at 12:00:02
In reply to Re: Never thought I'd hear this....., posted by linkadge on March 17, 2006, at 9:55:15
> > My point is this: The cluster of behaviors that >we see with the administration of amphetamine, >and that you have listed, is not a sufficient >criterion for true mania such that these >investigators needed to find other models to use.
> Some of the models we have today may not be conclusive, but I don't think that is reason to ignore them.
The only thing these models demonstrate is that psychostimulants can produce in animals the same behaviors that they produce in man. My belief (currently) is that what psychostimulants produce in a healthy (not bipolar) man is not mania. Neither do antidepressants produce these behaviors in animals. They only produce them in man in association with affective disorder. There are probably exceptions, of course. I contend that the majority of antidepressant-induced manias are those produced in people whom have a bipolar disorder and not a unipolar disorder. The citations you produced links to seem to support this. Unfortunately no single study was designed to test the specific question that we are debating: Does an antidepressant-induced mania usually indicate bipolar disorder, despite a lack of previous spontaneous episodes?
> > They judged the validity of their models based >upon the capacity of mood stabilizers to reverse >them. The hyperlocomotive and hyperlibidinal >effects produced by psychostimulants are thus >not equivalent to mania, and the presence of >these behaviors is not sufficient to presume a >valid animal model.
> Psychosis and mania have been effectively treated with drugs that were active in these paradigms.
Yes, but they are also active in models of schizophrenic psychosis. They don't seem to me to be specific for mania. Despite this, I will concede that it is possible to "light up" the manic areas of the brain in a healthy individual if, as Dr. Manji said, the conditions are right. The key question is, what are these conditions? Does using an SSRI as monotherapy qualify? That is what we are talking about here, as we are also talking about numbers. What is the percentage of people whom experience mania as a reaction to an SSRI that are bipolar? How do we determine this? Again, I think this issue can be resolved by performing a longitudinal study of people whom have had this reaction using life charting and prospective observation. At this time, I would argue that if there are other features of bipolarity present (including family history), then a manic reaction to an antidepressant indicates treating the person as if they were bipolar. I believe the chances of getting them well is enhanced by doing so.
> We can aruge that these behaviors aren't identical to human mania, but we could argue the same thing for rodent depression. That doesn't negate the fact that the model is oftentimes highly predictive of drug sucess in humans.
Definitely. But does that answer the clinical questions being pursued here?
> > Otherwise, I imagine they would have used >cocaine. So far, I don't believe that they have >been able to reproduce mania in rodents using >SSRIs.
> I don't know.
> > Hopefully, they will develop a strain of rodent that exhibits such a reaction so as to serve as a model for mania. Of course, this would only go to reinforce the notion that there must be a genetic bipolar diathesis present to >display a manic reaction to antidepressants.
> It is my contention that long term rat studies may show things that the short term ones don't. Rat studies are brief, but in yours and my mothers case, a manic reaction was not evident right away.It took at least 6 months to emerge. This is in contrast to stimulant-induced hyperlocomotive or psychotic states.
> > My mania lasted for weeks after the >antidepressants were discontinued, despite >lithium treatment.
> Hey I've got a good one for you. An interesting phenomina, is that sometimes severe manic episodes can happen upon *discontinuation* of an antidepressant.Not news to me. Happened to me 3 times with Nardil. The abstracts on the web page you cited demonstrate this and refer to the patients as being bipolar. I also experience an improvement when tricyclics are withdrawn quickly.
> Now would these people be bipolar? I would argue no. They are undergoing a dopamine rebound. Regular people + dopamine overflow = strange behavior.
We might be getting just a little too theoretical here to attend to the clinical question being asked.
> >I think this is one factor
> >that leads me to believe that a manic reaction >to antidepressants is fundamentally different >from the acute behavioral states produced by >psychostimulants. Mania involves a self->perpetuating process, most likely effected by >kindling and probably facilitated through second >messenger events.
> Stimulants can cause seizures in no time at all. I guess that implies they can cause kindling in no time at all too?If the seizure threshold for subsequent exposures is reduced, it obviously can.
I think this question relates to matters of threshold (sensitivity) and inertia (length of episode). How much exposure (dosage; time) is necessary for the manic event to occur? I imagine the threshold is lower for someone who is bipolar. There might not even be a threshold (too high a threshold) for someone who is healthy. How long will the reaction persist after the provocative medication is discontinued? I should think that in someone who is bipolar, the longer the mania is allowed to continue, the greater is its inertia and tendency to persist after drug discontinuation. The interesting question is whether or not an inertia can be kindled in someone whom is not bipolar. I imagine the rodent studies can be used as a model for this.
> > Again, Depakote would have prevented this as my >mania are very responsive to it. It is also >responsive to Zyprexa, but not to the older APs. >I should think that combining Nardil and Zyprexa >would be a great combination for bipolar >depression.
> Depakote can be helpfull. It has a stronger anti-kindling effect than lithium. Lithium can actually be proconvulsant.
You are a wealth of knowledge and understanding. I only wish my inability to read and remember things were equal to yours.
> I think that the moment we understand how these drugs work, is the moment we can quantify (with any certainty) how and why they fail.
By saying "how these drugs work", are you admitting that they do indeed work?
:-)
- Scott
Posted by SLS on March 17, 2006, at 12:17:39
In reply to Re: Never thought I'd hear this....., posted by Sobriquet Style on March 17, 2006, at 11:08:40
> The first line medications which are considered the best because they can stop cyling, are also the ones that cause the worst kind of flat effect in my opinon.
> Now, does the future hold a treatment with the same level of effect that can stop the cyling without the flatness? If I invested in pharmaceuticals, I'd certainly invest in that bipolar medication.
Right now, Lamictal is considered by many to have anti-cycling properties and is recommended for ultra-rapid cycling. I'd like to see how this plays out with the passage of time. Maybe it only works this way in conjunction with other mood stabilizers. The combination of Lithium + Lamictal is supposed to be much more effective as a prophylaxis against bipolar I disorder than lithium alone.
12.5mg of Lamictal?
Isn't it funny how some people respond to such low dosages of drugs. I wish I could get that kind of mileage out of Lamictal. It would be a much less costly habit.
Actually, I had been taking 300mg for several years. I eventually was able to reduce it to 100mg and retain most of the benefit. My reason for reducing the dosage was that I found that the higher dosages impaired my memory and ability to learn new things above and beyond the impairments produced by the depression itself.
- Scott
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